Status:
COMPLETED
Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer
Lead Sponsor:
National Cancer Institute (NCI)
Conditions:
Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This phase II trial is studying how well RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097) works in treating patients with previously treated metastatic pancreatic cancer. RO492...
Detailed Description
PRIMARY OBJECTIVES: I. To determine the 6-month survival of patients with previously treated metastatic pancreas cancer treated with gamma secretase RO4929097. II. To determine the adverse events of...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
- Not amenable to potentially curative surgical resection
- At least 1 prior regimen of chemotherapy, preferably gemcitabine-based, for metastatic disease
- Evidence of disease progression
- Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
- Available archived tumor tissue (baseline core biopsies or surgical tumor blocks)
- No diagnosis by fine-needle aspiration only
- No known brain metastases
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (Karnofsky 70-100%)
- White blood cell count (WBC) ≥ 3,000/mm³
- Absolute neutrophil count (ANC) ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Total bilirubin normal
- Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Willingness to undergo 2 tumor biopsies, if required
- Fertile patients must use 2 forms of contraception (i.e., barrier contraception and one other method of contraception) ≥ 4 weeks prior to, during, and for ≥ 12 months after completion of therapy
- Negative pregnancy test
- Not pregnant or nursing
- Able to swallow pills
- No patients with malabsorption syndrome or other condition that would interfere with intestinal absorption
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma secretase inhibitor RO4929097
- Not serologically positive for hepatitis A, B, or C
- No history of liver disease, other forms of hepatitis, or cirrhosis
- No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation
- No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia other than chronic, stable atrial fibrillation
- Psychiatric illness/social situations that would limit compliance with study requirements
- No baseline QTcF \> 450 msec (male) or QTcF \> 470 msec (female)
- No other malignancy within the past 5 years except curatively treated basal cell carcinoma of the skin or carcinoma in-situ of the uterine cervix
- No combination antiretroviral therapy for HIV-positive patients
- Recovered to \< Common Toxicity Criteria for Adverse Effects (NCI CTCAE) grade 2 toxicities from prior therapy
- More than 3 weeks since prior chemotherapy for metastatic disease (6 weeks for carmustine or mitomycin C)
- At least 4 weeks since prior radiotherapy
- Concurrent low-molecular weight heparin (LMWH) or full-dose coumadin allowed
- International normalized ratio (INR) must be monitored as clinically indicated
- No other concurrent investigational agents
- No concurrent strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers, including the following:
- Strong inhibitors: Amiodarone, erythromycin, clarithromycin, grapefruit juice, isoniazid, ketoconazole, itraconazole, or nefazodone
- Patients taken off strong inhibitors allowed provided they have ≥ 1-week washout period
- Strong inducers: Carbamazepine, pentobarbital, phenobarbital, phenytoin, Rifabutin, Rifampin, or St. John wort
- Patients taken off strong inducers allowed provided they have ≥ 2-week washout period
- No concurrent antiarrhythmics or other medications known to prolong QTc
Exclusion
Key Trial Info
Start Date :
October 1 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 1 2014
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT01232829
Start Date
October 1 2010
End Date
May 1 2014
Last Update
November 26 2014
Active Locations (3)
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1
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
2
University of Colorado
Denver, Colorado, United States, 80217-3364
3
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287